POS0954 CLINICAL FEATURES AND GENOMIC LANDSCAPE OF MYELOPROLIFERATIVE NEOPLASM (MPN) PATIENTS WITH AUTOIMMUNE AND INFLAMMATORY DISEASES
Authors: D. Elessa, L. P. Zhao, R. Daltro de Oliveira, N. Maslah, J. Soret-Dulphy, E. Verger, C. Marcault, N. Parquet, P. Fenaux, L. Adès, E. Raffoux, S. Giraudier, O. Fain, B. Cassinat, J. J. Kiladjian, A. Mekinian, L. Benajiba
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Autoimmune and inflammatory diseases (AID) are associated with myeloid malignancies<sup>[1]</sup>, and include both organ-specific diseases and systemic inflammatory disorders. While the occurrence of associated AID reaches up to 15-20% in myelodysplastic neoplasms (MDS) patients<sup>[2,3]</sup>, its prevalence in the context of myeloproliferative neoplasm (MPN) remains unknown. In patients with a history of AID, the risk of developing MPN was increased<sup>[4]</sup>, suggesting a correlative link between the two disorders, but data regarding the characterization of AID in MPN patients remain scarce and the lack of studies prevents from identifying potential risk traits that may underline a common physiopathology. <h3>Objectives</h3> We conducted a single center retrospective study to describe the prevalence, clinical and biological features of AID in MPN patients. We also reported the mutational landscape of MPN with associated AID, along with its prognostic impact. <h3>Methods</h3> All patients with a diagnosis of Philadelphia-negative MPN according to the World Health Organization's criteria, followed between January 2011 and January 2021 in our center were included. Clinical and biological characteristics at the time of diagnosis and follow-up were collected. Next-generation targeted sequencing was performed targeting a panel of 36 genes involved in myeloid malignancies. AID diagnosis was based on recommended international criteria specific to each AID. Patients with interferon-alpha-induced AID were excluded from this study. <h3>Results</h3> A total of 1541 MPN patients were included, including 95 (6%) patients with AID who were compared to the remaining 1446 (94%) patients without AID. Median age was 51.6 [6.6; 98.3] years at MPN diagnosis in the whole cohort. Female patients were predominant within the AID group (62 (65%) versus 773 (54%), p=0.03). Within the AID cohort, a total of 103 diagnoses of AID were reported in 95 patients, including 48 organ-specific AID (47%) (autoimmune hypothyroidism (n=33), inflammatory bowel diseases (IBD, n=7), neuroinflammatory disorders (n=4), autoimmune cytopenia (n=2), glomerulonephritis (n=1) and pernicious anemia (n=1)), 13 inflammatory arthritis (13%), 9 connective tissue diseases (9%), 9 dermatosis (9%), 6 systemic vasculitis (6%) and 18 unclassified AID (17%). Molecular sequencing was performed in 998/1541 (65%) patients and the prevalence of driver and additional mutations did not differ between the MPN with or without AID. The prevalence of <i>TET2</i> mutations was higher in the AID cohort (21/65, 32% versus 208/993, 22%), although not reaching statistical significance (p=0.08). After a median follow-up of 8.3 <sub>IQR</sub>[3.7-14.3] years, the association with AID did not impact overall survival (p= 0.67), MDS/AML transformation free survival (p=0.37) or secondary myelofibrosis-free survival (p=0.91). <h3>Conclusion</h3> Our data suggest that the prevalence of AID is similar in MPN patients to that of the general population, and that the distribution and presentation of AID in MPN patients is also similar. <i>TET2</i> mutations are highly prevalent in MPN patients with AID suggesting a shared physiopathology. Additional mechanistic studies are needed to further decipher a potential TET2-mediated common physiopathology. The association with AID did not impact MPN patients' outcome. <h3>References</h3> [1]Barcellini, W. <i>et al.</i> Increased prevalence of autoimmune phenomena in myelofibrosis: Relationship with clinical and morphological characteristics, and with immunoregulatory cytokine patterns. <i>Leukemia Research</i><b>37</b>, 1509–1515 (2013). [2]Mekinian, A. <i>et al.</i> Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study. <i>Rheumatology (Oxford</i>) <b>55</b>, 291–300 (2016). [3]Zhao, L.-P. <i>et al.</i> Genomic landscape of MDS/CMML associated with systemic inflammatory and autoimmune disease. <i>Leukemia</i> (2021). [4]Kristinsson, S. Y. <i>et al</i>. Autoimmunity and the risk of myeloproliferative neoplasms. <i>Haematologica</i><b>95</b>, 1216–1220 (2010). <h3>Acknowledgements</h3> The authors thank the clinical care team of the Comprehensive Myeloproliferative neoplasms Center for samples and data collection, and the staff of the cellular biology laboratory for excellent technical assistance. The authors also thank the French Intergroup for Myeloproliferative neoplasms (FIM) for insightful discussions. <h3>Disclosure of Interests</h3> None Declared.